The revision partial knee classification system: understanding the causative pathology and magnitude of further surgery following partial knee arthroplasty.

AIMS: Joint registries classify all further arthroplasty procedures to a knee with an existing partial arthroplasty as revision surgery, regardless of the actual procedure performed. Relatively minor procedures, including bearing exchanges, are classified in the same way as major operations requiring augments and stems. A new classification system is proposed to acknowledge and describe the detail of these procedures, which has implications for risk, recovery, and health economics. METHODS: Classification categories were proposed by a surgical consensus group, then ranked by patients, according to perceived invasiveness and implications for recovery. In round one, 26 revision cases were classified by the consensus group. Results were tested for inter-rater reliability. In round two, four additional cases were added for clarity. Round three repeated the survey one month later, subject to inter- and intrarater reliability testing. In round four, five additional expert partial knee arthroplasty surgeons were asked to classify the 30 cases according to the proposed revision partial knee classification (RPKC) system. RESULTS: Four classes were proposed: PR1, where no bone-implant interfaces are affected; PR2, where surgery does not include conversion to total knee arthroplasty, for example, a second partial arthroplasty to a native compartment; PR3, when a standard primary total knee prosthesis is used; and PR4 when revision components are necessary. Round one resulted in 92% inter-rater agreement (Kendall's W 0.97; p < 0.005), rising to 93% in round two (Kendall's W 0.98; p < 0.001). Round three demonstrated 97% agreement (Kendall's W 0.98; p < 0.001), with high intra-rater reliability (interclass correlation coefficient (ICC) 0.99; 95% confidence interval 0.98 to 0.99). Round four resulted in 80% agreement (Kendall's W 0.92; p < 0.001). CONCLUSION: The RPKC system accounts for all procedures which may be appropriate following partial knee arthroplasty. It has been shown to be reliable, repeatable and pragmatic. The implications for patient care and health economics are discussed. Cite this article: Bone Jt Open 2021;2(8):638-645

An adeno-associated viral vector transduces the rat hypothalamus and amygdala more efficient than a lentiviral vector

<p>Abstract</p> <p>Background</p> <p>This study compared the transduction efficiencies of an adeno-associated viral (AAV) vector, which was pseudotyped with an AAV1 capsid and encoded the green fluorescent protein (GFP), with a lentiviral (LV) vector, which was pseudotyped with a VSV-G envelop and encoded the discosoma red fluorescent protein (dsRed), to investigate which viral vector transduced the lateral hypothalamus or the amygdala more efficiently. The LV-dsRed and AAV1-GFP vector were mixed and injected into the lateral hypothalamus or into the amygdala of adult rats. The titers that were injected were 1 × 10⁸or 1 × 10⁹genomic copies of AAV1-GFP and 1 × 10⁵transducing units of LV-dsRed.</p> <p>Results</p> <p>Immunostaining for GFP and dsRed showed that AAV1-GFP transduced significantly more cells than LV-dsRed in both the lateral hypothalamus and the amygdala. In addition, the number of LV particles that were injected can not easily be increased, while the number of AAV1 particles can be increased easily with a factor 100 to 1000. Both viral vectors appear to predominantly transduce neurons.</p> <p>Conclusions</p> <p>This study showed that AAV1 vectors are better tools to overexpress or knockdown genes in the lateral hypothalamus and amygdala of adult rats, since more cells can be transduced with AAV1 than with LV vectors and the titer of AAV1 vectors can easily be increased to transduce the area of interest.</p

Neuropeptide delivery to the brain: a von Willebrand factor signal peptide to direct neuropeptide secretion

<p>Abstract</p> <p>Background</p> <p>Multiple neuropeptides, sometimes with opposing functions, can be produced from one precursor gene. To study the roles of the different neuropeptides encoded by one large precursor we developed a method to overexpress minigenes and establish local secretion.</p> <p>Results</p> <p>We fused the signal peptide from the Von Willebrand Factor (VWF) to a furin site followed by a processed form of the Agouti related protein (AgRP), AgRP_83-132or α-melanocyte stimulating hormone. <it>In vitro</it>, these minigenes were secreted and biologically active. Additionally, the proteins of the minigenes were not transported into projections of primary neurons, thereby ensuring local release. <it>In vivo </it>administration of VWF-AgRP_83-132, using an adeno-associated viral vector as a delivery vehicle, into the paraventricular hypothalamus increased body weight and food intake of these rats compared to rats which received a control vector.</p> <p>Conclusions</p> <p>This study demonstrated that removal of the N-terminal part of full length AgRP and addition of a VWF signal peptide is a successful strategy to deliver neuropeptide minigenes to the brain and establish local neuropeptide secretion.</p

Molecular Dynamics Analysis of Apolipoprotein-D - Lipid Hydroperoxide Interactions: Mechanism for Selective Oxidation of Met-93

Background: Recent studies suggest reduction of radical-propagating fatty acid hydroperoxides to inert hydroxides by interaction with apolipoprotein-D (apoD) Met93 may represent an antioxidant function for apoD. The nature and structural consequences of this selective interaction are unknown. Methodology/Principal Findings: Herein we used molecular dynamics (MD) analysis to address these issues. Longtimescale simulations of apoD suggest lipid molecules are bound flexibly, with the molecules free to explore multiple conformations in a binding site at the entrance to the classical lipocalin ligand-binding pocket. Models of 5s- 12s- and 15s hydroperoxyeicosatetraenoic acids were created and the lipids found to wrap around Met93 thus providing a plausible mechanism by which eicosatetraenoic acids bearing hydroperoxides on different carbon atoms can interact with Met93 to yield Met93 sulfoxide (Met93SO). Simulations of glycosylated apoD indicated that a second solvent exposed Met at position 49 was shielded by a triantennerary N-glycan attached to Asn45 thereby precluding lipid interactions. MD simulations of apoD showed B-factors of the loop containing Met93SO were higher in the oxidized protein, indicating increased flexibility that is predicted to destabilize the protein and promote self-association. Conclusions/Significance: These studies provide novel insights into the mechanisms that may contribute to the antioxidant function of apoD and the structural consequences that result if Met93SO is not redox-cycled back to its native state

BR-squared: a practical solution to the winner’s curse in genome-wide scans

The detrimental effects of the winner’s curse, including overestimation of the genetic effects of associated variants and underestimation of sufficient sample sizes for replication studies are well-recognized in genome-wide association studies (GWAS). These effects can be expected to worsen as the field moves from GWAS into whole genome sequencing. To date, few studies have reported statistical adjustments to the naive estimates, due to the lack of suitable statistical methods and computational tools. We have developed an efficient genome-wide non-parametric method that explicitly accounts for the threshold, ranking, and allele frequency effects in whole genome scans. Here, we implement the method to provide bias-reduced estimates via bootstrap re-sampling (BR-squared) for association studies of both disease status and quantitative traits, and we report the results of applying BR-squared to GWAS of psoriasis and HbA1c. We observed over 50% reduction in the genetic effect size estimation for many associated SNPs. This translates into a greater than fourfold increase in sample size requirements for successful replication studies, which in part explains some of the apparent failures in replicating the original signals. Our analysis suggests that adjusting for the winner’s curse is critical for interpreting findings from whole genome scans and planning replication and meta-GWAS studies, as well as in attempts to translate findings into the clinical setting

A meta-analytic review of stand-alone interventions to improve body image

Objective Numerous stand-alone interventions to improve body image have been developed. The present review used meta-analysis to estimate the effectiveness of such interventions, and to identify the specific change techniques that lead to improvement in body image. Methods The inclusion criteria were that (a) the intervention was stand-alone (i.e., solely focused on improving body image), (b) a control group was used, (c) participants were randomly assigned to conditions, and (d) at least one pretest and one posttest measure of body image was taken. Effect sizes were meta-analysed and moderator analyses were conducted. A taxonomy of 48 change techniques used in interventions targeted at body image was developed; all interventions were coded using this taxonomy. Results The literature search identified 62 tests of interventions (N = 3,846). Interventions produced a small-to-medium improvement in body image (d+ = 0.38), a small-to-medium reduction in beauty ideal internalisation (d+ = -0.37), and a large reduction in social comparison tendencies (d+ = -0.72). However, the effect size for body image was inflated by bias both within and across studies, and was reliable but of small magnitude once corrections for bias were applied. Effect sizes for the other outcomes were no longer reliable once corrections for bias were applied. Several features of the sample, intervention, and methodology moderated intervention effects. Twelve change techniques were associated with improvements in body image, and three techniques were contra-indicated. Conclusions The findings show that interventions engender only small improvements in body image, and underline the need for large-scale, high-quality trials in this area. The review identifies effective techniques that could be deployed in future interventions

A case study of bovine tuberculosis in an area of County Donegal, Ireland

A descriptive analysis, to investigate the potential risk factors that might have contributed to the increased incidence of bovine tuberculosis (BTB) herd-breakdowns in the reference area of Co. Donegal during the fifth year of the four-area project (FAP), was performed. Seventy two different herds were restricted for BTB during the FAP; 10 of these herds were restricted twice, resulting in a total of 82 BTB breakdowns. During the first four years of the FAP, the number of BTB herd breakdowns in the area varied from a lowest of nine to a maximum of 18 per year, and were geographically dispersed. In the fifth year of the study a considerable increase in the number of BTB breakdowns (n = 32) was observed, and there was a spatial 'cluster' of infected herds in the eastern part of the study area. The increased number of BTB breakdowns during the fifth year most likely occurred because of the recrudescence of infection, herd-to-herd transmission and, to a lesser extent, purchase of infected cattle. Infected badgers remain as a possible but less likely source of infection, especially as an explanation for the cluster of infected herds. The analysis supports the hypothesis that BTB in herds is a problem that cannot be addressed successfully by dedicating our efforts to the elimination of single risk factors. Neither is it a problem that needs to be investigated only at the herd level, but rather at the area level, including groups of contiguous herds

The utilisation of health research in policy-making: Concepts, examples and methods of assessment

The importance of health research utilisation in policy-making, and of understanding the mechanisms involved, is increasingly recognised. Recent reports calling for more resources to improve health in developing countries, and global pressures for accountability, draw greater attention to research-informed policy-making. Key utilisation issues have been described for at least twenty years, but the growing focus on health research systems creates additional dimensions. The utilisation of health research in policy-making should contribute to policies that may eventually lead to desired outcomes, including health gains. In this article, exploration of these issues is combined with a review of various forms of policy-making. When this is linked to analysis of different types of health research, it assists in building a comprehensive account of the diverse meanings of research utilisation. Previous studies report methods and conceptual frameworks that have been applied, if with varying degrees of success, to record utilisation in policy-making. These studies reveal various examples of research impact within a general picture of underutilisation. Factors potentially enhancing utilisation can be identified by exploration of: priority setting; activities of the health research system at the interface between research and policy-making; and the role of the recipients, or 'receptors', of health research. An interfaces and receptors model provides a framework for analysis. Recommendations about possible methods for assessing health research utilisation follow identification of the purposes of such assessments. Our conclusion is that research utilisation can be better understood, and enhanced, by developing assessment methods informed by conceptual analysis and review of previous studies

Integration of Consonant and Pitch Processing as Revealed by the Absence of Additivity in Mismatch Negativity

Consonants, unlike vowels, are thought to be speech specific and therefore no interactions would be expected between consonants and pitch, a basic element for musical tones. The present study used an electrophysiological approach to investigate whether, contrary to this view, there is integrative processing of consonants and pitch by measuring additivity of changes in the mismatch negativity (MMN) of evoked potentials. The MMN is elicited by discriminable variations occurring in a sequence of repetitive, homogeneous sounds. In the experiment, event-related potentials (ERPs) were recorded while participants heard frequently sung consonant-vowel syllables and rare stimuli deviating in either consonant identity only, pitch only, or in both dimensions. Every type of deviation elicited a reliable MMN. As expected, the two single-deviant MMNs had similar amplitudes, but that of the double-deviant MMN was also not significantly different from them. This absence of additivity in the double-deviant MMN suggests that consonant and pitch variations are processed, at least at a pre-attentive level, in an integrated rather than independent way. Domain-specificity of consonants may depend on higher-level processes in the hierarchy of speech perception

Identification of a biomarker panel for improvement of prostate cancer diagnosis by volatile metabolic profiling of urine

Background: The lack of sensitive and specific biomarkers for the early detection of prostate cancer (PCa) is a major hurdle to improve patient management. Methods: A metabolomics approach based on GC-MS was used to investigate the performance of volatile organic compounds (VOCs) in general and, more specifically, volatile carbonyl compounds (VCCs) present in urine as potential markers for PCa detection. Results: Results showed that PCa patients (n = 40) can be differentiated from cancer-free subjects (n = 42) based on their urinary volatile profile in both VOCs and VCCs models, unveiling significant differences in the levels of several metabolites. The models constructed were further validated using an external validation set (n = 18 PCa and n = 18 controls) to evaluate sensitivity, specificity and accuracy of the urinary volatile profile to discriminate PCa from controls. The VOCs model disclosed 78% sensitivity, 94% specificity and 86% accuracy, whereas the VCCs model achieved the same sensitivity, a specificity of 100% and an accuracy of 89%. Our findings unveil a panel of 6 volatile compounds significantly altered in PCa patients' urine samples that was able to identify PCa, with a sensitivity of 89%, specificity of 83%, and accuracy of 86%. Conclusions: It is disclosed a biomarker panel with potential to be used as a non-invasive diagnostic tool for PCa.info:eu-repo/semantics/publishedVersio